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Birgitta Henriques Normark

Publications and source records attributed to Birgitta Henriques Normark.

14 recordsLinked to original sources
PubMed2006

Modeling the regulation of the competence-evoking quorum sensing network in Streptococcus pneumoniae.

Competence for genetic transformation seems to play a fundamental role in the biology of Streptococcus pneumoniae and is believed to account for serotype switching, evolution of virulence factors, and rapid emergence of antibiotic resistance. The initiation of competence is regulated by the quorum sensing system referred as the ComABCDE pathway. Experimental studies reveal that competence is down-regulated a short time after its induction and several hypotheses about the mechanism(s) responsible for this shut-down have been presented. Possibly, a ComX-dependent gene product, such as a repressor or a phosphatase, is involved. To better understand the down-regulation of the competence-evoking system in S. pneumoniae, a mathematical model was set up. By analyzing the model, we suggest that shut-down of competence possibly occurs at the transcriptional level on the comCDE operon. As a result of introducing a putative comX-dependent repressor, which inhibits expression of comCDE and comX, in the mathematical model, competence is demonstrated to appear in waves. This is supported by experimental studies showing the appearance of successive competence cycles in pneumococcal batch cultures.

Antigens, Bacterial↗
PubMed2006

Penicillin-resistant pneumococci in Sweden 1997-2003: increased multiresistance despite stable prevalence and decreased antibiotic use.

Antimicrobial resistance patterns and capsular groups of penicillin-resistant Streptococcus pneumoniae (PRP; MIC penicillin G > or = 0.5 mg/ml) in Sweden between 1997 and 2003 were described, and trends in resistance and antibiotic sales during the same period were compared. The most common serogroups were in descending order 9, 19, 14, 23, and 6. Despite a low and stable annual PRP rate (proportion of PRP out of all pneumococci) of around 2% during the study period, the proportion of PRP resistant to other antibiotics increased. Of all tested PRP isolates, 82% were also resistant to trimethoprim/sulfamethoxazole, 32% had additional resistance to tetracycline, and 26% to erythromycin. Antibiotic sales figures for all studied antibiotic subgroups decreased during the same period. Little correlation was found between antibiotic sales and PRP resistance rates, indicating that there are still other poorly defined factors contributing to the reported resistance levels in the population. However, although PRP strains in Sweden are becoming more commonly resistant to antibiotics other than beta-lactams, the low and further reduced antibiotic sales still might have delayed the development and rapid spread of PRP in the population.

Adolescent↗
PubMed2005

Myeloid differentiation factor 88-dependent signalling controls bacterial growth during colonization and systemic pneumococcal disease in mice.

The Toll-like receptors (TLRs) and the myeloid differentiation factor 88 (MyD88) are key players in the activation of the innate immune defence during microbial infections. Using different murine infection models, we show that MyD88-dependent signalling is crucial for the activation of the innate immune defence against Streptococcus pneumoniae. Our data demonstrate that both local and systemic inflammatory response to S. pneumoniae depends on the presence of MyD88 to clear bacterial colonization of the upper respiratory tract and to prevent pulmonary and systemic infection in mice. Finally, we described a strong correlation between enhanced bacterial growth in the bloodstream of MyD88-deficient mice and the inability to lower the serum iron concentration in response to infection.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Differences in potency of intravenous polyspecific immunoglobulin G against streptococcal and staphylococcal superantigens: implications for therapy of toxic shock syndrome.

Administration of intravenous polyspecific immunoglobulin G (IVIG) has been proposed as adjunctive therapy for toxic shock syndrome caused by Streptococcus pyogenes or Staphylococcus aureus. We investigated whether superantigen-containing culture supernatants prepared from streptococcal isolates (n=21) and staphylococcal isolates (n=20) from cases of severe sepsis were inhibited to an equal extent by IVIG in proliferation experiments that used human peripheral blood mononuclear cells. All 3 IVIG preparations tested were highly efficient in neutralizing the superantigens, and most supernatants were completely inhibited at concentrations ranging from 0.05 to 2.5 mg IVIG/mL. An important finding was that culture supernatants from S. pyogenes isolates were consistently inhibited to a greater extent than those of S. aureus isolates (P<.01). The findings demonstrate that staphylococcal superantigens are not inhibited as efficiently as streptococcal superantigens by IVIG, and, hence, a higher dose of IVIG may be required for therapy of staphylococcal toxic shock syndrome in order to achieve protective titers and clinical efficacy.

Humans↗
PubMed2004

The impact of active intervention on the spread of penicillin-resistant Streptococcus pneumoniae in Swedish day-care centres.

Policies for handling cases of penicillin-non-susceptible Streptococcus pneumoniae (PNSP) in day-care groups vary between different counties in Sweden. The aim of this study was to evaluate the epidemiological effect of excluding PNSP-carriers from children's day-care centres (DCC). We followed the incidence in 14 DCC groups with ongoing PNSP-spread, by repeated group screens until no further cases could be identified. All identified carriers were excluded from DCC attendance in study area A (Skåne region) while they remained in the group in study area B (Göteborg and örebro), according to local policies. The intervention effect was evaluated by comparing the number of additional cases after the baseline screen (start of the intervention period) between the 2 study areas. All PNSP-isolates were characterized by resistance pattern, serotype and pulse-field gel electrophoresis. The relative risk for children in DCCs without active intervention was 6.4 (95% CI: 2.0-20.7). Each prevented case in area A can be estimated to have demanded the exclusion of 2 other children from day care for approximately 4 weeks each. The total cost-benefit outcome of this action has to be seen in the light of the local situation with regard to the population prevalence and the distribution of other risk factors.

Age Distribution↗
PubMed2003

Capsular expression in Streptococcus pneumoniae negatively affects spontaneous and antibiotic-induced lysis and contributes to antibiotic tolerance.

Penicillin and vancomycin induce a lytic response in Streptococcus pneumoniae that requires the N-acetylmuramyl-l-alanine amidase LytA. We show that clinical isolates of pneumococci of capsular serotypes 1, 4, 6B, and 23F were generally less lytic to penicillin than pneumococci of serotypes 14 and 3. In addition, most 9V isolates were less lytic to vancomycin, compared with isolates of other serotypes. Parent-mutant pairs expressing and not expressing capsular serotypes 2, 4, and 9V were compared for antibiotic-induced lysis. The nonencapsulated variants were considerably more lytic after beta-lactam and/or vancomycin treatment, and antibiotic tolerance was seen only in the context of capsule expression. Conversion from a nonlytic to a lytic phenotype, after loss of capsule expression, required an intact lytA autolysin gene. Exogenous addition of purified LytA gave a lower lytic response in capsulated strains, compared with that in nonencapsulated mutants. Spontaneous autolysis in stationary phase also was negatively affected by capsule expression in an autolysin-dependent manner. Long-term starvation in the stationary phase of the vancomycin- and penicillin-tolerant isolate I95 yielded nonencapsulated mutants that had lost antibiotic tolerance and were lytic to penicillin and vancomycin. The 9V capsular locus of I95 and one of these stationary phase-selected mutants were completely sequenced. The only difference found was a 1-bp frameshift deletion in the cps9vE gene of the lytic mutant, encoding a uridine diphosphate-glucosyl-1-phosphate transferase. Two additional independently isolated lytic mutants of I95 from the stationary phase also contained mutations in the same region of cps9vE, which identified it as a mutational hot spot. This report demonstrates that capsular polysaccharides negatively influence the lytic process and contribute to antibiotic tolerance in clinical isolates of pneumococci.

Anti-Bacterial Agents↗
PubMed2003

Toxin-gene profile heterogeneity among endemic invasive European group A streptococcal isolates.

We determined the toxin-gene profiles of 239 endemic, invasive group A streptococcal (GAS) isolates that circulated, within a 5-year period, in European university hospitals. Profiling was performed by use of multiplex polymerase chain reaction that screened for 9 streptococcal pyrogenic exotoxins (speA, speB, speC, speF, speG, speH, speJ, ssa, and smeZ). Analysis revealed that invasive GAS isolates do not share a common toxin-gene profile. Although all emm types were characterized by several different toxin-gene profiles, a predominance of 1 or 2 toxin-gene profiles could be observed, reflecting that a few invasive clones have spread successfully throughout the world. Remarkably, statistical pair-wise analysis of individual toxin genes revealed that strains that did not share the predominant profile still showed a nonrandom distribution of key toxin genes characteristic of the specific emm type. This could indicate that M proteins function, directly or indirectly, as barriers for horizontal gene exchange.

Antigens, Bacterial↗
PubMed2003

Intracellular recognition of lipopolysaccharide by toll-like receptor 4 in intestinal epithelial cells.

Toll-like receptor (TLR)4 has recently been shown to reside in the Golgi apparatus of intestinal crypt epithelial m-ICcl2 cells, colocalizing with internalized lipopolysaccharide (LPS). Here we demonstrate that disruption of the integrity of the Golgi apparatus significantly reduced LPS-mediated nuclear factor kappaB activation. Also, the TLR4 adaptor protein MyD88 and the serine/threonine kinase IRAK-1 were rapidly recruited to the Golgi apparatus upon stimulation. LPS-mediated activation required lipid raft formation and intact clathrin-dependent internalization. In contrast to macrophages, prevention of ligand internalization by use of LPS-coated beads significantly impaired recognition by epithelial cells. The localization of TLR4 to the Golgi apparatus was abrogated by expression of a genetically modified form of the TLR4 binding chaperone gp96. Thus, our data provide evidence that in contrast to the situation in macrophages, LPS recognition in intestinal epithelial cells may occur in the Golgi apparatus and require LPS internalization.

Animals↗
PubMed2003

Group A streptococcal infections in Sweden: a comparative study of invasive and noninvasive infections and analysis of dominant T28 emm28 isolates.

Surveillance of group A streptococcus (GAS) infections in Sweden during 1996-1997 indicated that T28 isolates were dominant, whereas T1M1 infections were uncommon. Circulating T28 isolates were nearly all emm28, MLST52, and these clones had also been prevalent 10 years earlier. Isolates from invasive and noninvasive infections were of similar types and prevalences. The average national incidence of invasive episodes was 2.9/100,000 population but varied between 0 and 8.3/100,000 population in different counties. It increased markedly with age, reaching 22.9 episodes/100,000 among people aged > or =90 years. The incidence of puerperal sepsis was higher than expected (22.4/100,000 of those at risk), with 1 death. Overall mortality was 16% and was associated with preexisting chronic disease (P=.002). Streptococcal toxic shock syndrome (STSS) developed in approximately 15% of patients with invasive episodes, with a mortality rate of 45%. The use of nonsteroidal anti-inflammatory drugs was not found to be associated with the development of STSS.

Age Distribution↗
PubMed2003

Persistent infection with Helicobacter pylori and the development of gastric cancer.

Gastric malignancies have been closely linked to infection of the gastric mucosa with Helicobacter pylori, but the individual factors involved in the multistage process of tumor development are still poorly understood. H. pylori evades the host defense system and causes persistent infection and chronic inflammation. Immune activation leads to DNA damage by the release of oxygen and nitrogen radicals. Ongoing tissue repair mechanisms and the secretion of cytokines and growth factors, as well as bacterial effector molecules, cause disturbances in the balance between epithelial cell proliferation and apoptosis, promote the accumulation of potential oncogenic mutations, and support neovascularization and tumor growth. In addition, H. pylori might hamper the development of an efficient antitumor immunity and provoke immune-mediated pathology. This review summarizes the recent progress in the understanding of the intimate bacteria-host relationship and the mechanisms by which H. pylori may promote the process of tumor development.

Apoptosis↗
PubMed2003

Capsular types and antibiotic susceptibility of invasive Streptococcus pneumoniae among children in Sweden.

To investigate the serotype distribution and antibiotic susceptibility patterns 204 isolates of Streptococcus pneumoniae obtained from blood or cerebrospinal fluid (CSF) of children < or = 18 y of age were collected from 19 clinical microbiological laboratories in Sweden during the years 1998-2001. 166 isolates were from blood only, and 38 isolates were from CSF. The most common serotypes found were 6B, 1, 7F, 14, 18C, 19F, 6A, 4, 23F, 9V and 19A, in descending order of frequency. During the study period serotype 6B increased in frequency from 14.3% in 1998 to 28.3% in 2001 and serotype 1 decreased simultaneously from 20.4% to 9.4%. Serotype 1 was the most common serotype among children > or = 2 y of age or older, but was not found among children < 2 y of age. The potential coverage rate for the heptavalent pneumococcal conjugate vaccine varied between 53 and 68% during the studied years, and was higher for children < 2 y of age (74%) than for older children (51%). The majority of isolates were susceptible to penicillin and other antibiotics tested.

Age Factors↗